Hypopigmentation disorders are characterized by impaired melanogenesis and remain challenging to manage due to limited efficacy of current interventions and insufficient mechanistic insights. Natural products represent a valuable source of bioactive phytoconstituents capable of regulating key pathways involved in melanin synthesis. Despite its extensive traditional use and diverse pharmacological activities, Tinospora cordifolia and its major bioactive constituent tinosporide remain unexplored for their role in melanogenesis. The present study aimed to evaluate the melanogenesis-promoting potential of bioactive phytoconstituents isolated from Tinospora cordifolia, and to elucidate their underlying molecular mechanisms. Four phytoconstituents–columbin, tinosporide, 8-hydroxy tinosporide and ecdysterone–were isolated and structurally characterized from T. cordifolia. Their melanogenic potential was evaluated in murine (B16F10) and human (SK-MEL-2) melanoma cells by assessing melanin content, tyrosinase activity, and expression of melanogenesis-associated genes. Intracellular cAMP levels and associated signalling pathways were further analysed to investigate the mechanism of action. Among the isolated compounds, tinosporide exhibited the most pronounced melanogenic activity, significantly increasing melanin synthesis and tyrosinase activity. Tinosporide promotes nuclear localization of the microphthalmia-associated transcription factor (MITF), leading to upregulation of MITF-target genes, including Trp1, Tyr, Dct, Pmel, and Mlana. Furthermore, mechanistic studies revealed that tinosporide elevated intracellular cAMP levels and induced the phosphorylation of PKA and CREB, thereby activating cAMP/PKA/CREB signalling pathway. Pharmacological inhibition of PKA and CREB markedly attenuated tinosporide-induced melanogenesis, confirming the essential role of the cAMP/PKA/CREB–MITF axis. Collectively, these findings identify tinosporide as a promising natural melanogenic agent derived from Tinospora cordifolia and highlight its potential relevance in the development of plant-based interventions for hypopigmentation disorders.

Introduction: Epigallocatechin-3-gallate (EGCG) and Curcumin (CUR), the primary active components in Green Tea Extract (GTE) and Turmeric Extract (TE), respectively, have shown efficacy in the treatment of psoriasis. An antipsoriatic thermoresponsive in-situ gel containing both extracts has been developed in-house. However, simultaneous estimation of these drugs from the dosage form is challenging due to overlapping spectra. Aim: To develop and validate simple, efficient, and environment friendly spectrophotometric methods for the simultaneous estimation of EGCG and CUR in the developed formulation. Materials and Methods: Vierordt’s equation method, quotient absorbance ratio method, and dual-wavelength method were developed. The wavelength maxima (λmax) of CUR was found at 425 nm, where interference from EGCG was negligible at lower concentrations, whereas at 276 nm (λ max of EGCG), CUR showed significant interference. The isosbestic point was observed at 300 nm, and wavelengths of 276 nm and 310 nm were selected for the dual-wavelength method. Laboratory-prepared mixtures were analyzed to assess reliability, followed by application to the formulation. Validation was performed as per International Council for Harmonisation guidelines. Results: The methods demonstrated acceptable accuracy, precision, and reliability for simultaneous estimation of EGCG and CUR. Validation parameters were within acceptable limits. Greenness assessment using the Analytical Greenness metric approach and the Green Assessment Profile Index indicated satisfactory environmental performance. Conclusion: The proposed methods provide a simple, cost-effective, and environmentally sustainable approach for routine analysis of EGCG and CUR in thermoresponsive in-situ gel formulations.

Background: Turmeric ( Curcuma longa L.) and Green tea ( Camellia sinensis [L.] Kuntze) have a long history of traditional use in Ayurveda due to their potent antioxidant action in managing several skin conditions. Aims and Objectives: To evaluate the synergistic effects of Turmeric Extract (TE) and Green Tea Extract (GTE) on key enzymes related to skin aging, pigmentation, and inflammation. The primary objective was to investigate and assess the synergistic effect of both extracts on target enzymes, thereby achieving significant efficacy with a minimal concentration of individual drugs, thereby reducing the risk of side effects and providing a basis for the development of an effective skin-care formulation. Materials and Methods: Inhibition against collagenase, elastase, hyaluronidase, and tyrosinase was tested using enzyme inhibition assays, and the anti-inflammatory potential was tested through cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) inhibition. The study also evaluated the antioxidant activity through 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), Ferric Reducing Antioxidant Power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl assays. A synergistic action of both extracts was established using CompuSyn software against each target enzyme. The in vitro cytotoxicity of the extracts on the 3T3 and L929 fibroblast cells was determined to establish the safety profile of the extracts. Results: Both TE and GTE presented significant inhibitory activities against all tested enzymes in a dose-dependent manner. A 1:1 (w/w) mixed preparation of TE and GTE showed synergistic activities compared to each single compound, as shown by a Combination Index of < 1 computed using CompuSyn. The best inhibition of collagenase was obtained with the combination (IC 50 = 7.94 μg/ml) and elastase (IC 50 = 4.29 μg/ml), including enzymes crucial for skin elasticity. Tyrosinase inhibition (IC 50 = 26.05 μg/ml) holds some promising prospects regarding pigment control. Finally, the considerable COX-2 and LOX inhibition (IC 50 = 1.98 μg/ml and 14.02 μg/ml, respectively) evidently confirms good anti-inflammatory ability in these extracts. The cytotoxicity tests had confirmed that the extracts are nontoxic over the entire tested concentration range. Conclusion: Results showcase the combination of TE and GTE as promising agents in the direction of antiaging, antipigmentation, and anti-inflammatory skincare applications. The synergistic activity between extracts could allow them to be used at lower doses without losing their efficacy; in this respect, they seem to be an interesting alternative for natural skincare formulations.

The rising geriatric population is expected to increase the demand for drugs treating neurodegenerative diseases. The present work is aimed to discover acetylcholinesterase (AChE) inhibitors from Cissampelos pareira Linn. aerial parts (Family: Menispermaceae). Bioassay-guided isolation, AChE inhibition study and estimation of the therapeutic marker in different parts of raw herbs were conducted. The structure of the compound (1) was elucidated as N-methylneolitsine by using NMR (1D and 2D) and ESI-MS/MS spectral data, which is a new natural analogue of neolitsine. It showed good AChE inhibition with an IC50 value of 12.32 mu g/mL. It was densitometrically estimated to be 0.074 - 0.33% in aerial parts of C. pareira, collected from various locations. The alkaloid reported here could be potentially useful for the treatment of various neurodegenerative diseases and the aerial part of C. pareira could be used as a promising ingredient for various preparations treating neurodegenerative diseases.

Rheumatoid arthritis is a chronic autoimmune inflammatory disease characterized by immune response overexpression, causing pain and swelling in the synovial joints. This condition is caused by auto-reactive antibodies that attack self-antigens due to their incapacity to distinguish between self and foreign molecules. Dysregulated activity within numerous signalling and immunological pathways supports the disease's development and progression, elevating its complexity. While current treatments provide some alleviation, their effectiveness is accompanied by a variety of adverse effects that are inherent in conventional medications. As a result, there is a deep-rooted necessity to investigate alternate therapeutic strategies capable of neutralizing these disadvantages. Medicinal herbs display a variety of potent bioactive phytochemicals that are effective in the complementary management of disease, thus generating an enormous potency for the researchers to delve deep into the development of novel phytomedicine against autoimmune diseases, although additional evidence and understanding are required in terms of their efficacy and pharmacodynamic mechanisms. This literature-based review highlights the dysregulation of immune tolerance in rheumatoid arthritis, analyses the pathophysiology, elucidates relevant signalling pathways involved, evaluates present and future therapy options and underscores the therapeutic attributes of a diverse array of medicinal herbs in addressing this severe disease.

BACKGROUND:Understanding the evolutionary history of plants and accurately identifying biologically important species and their families is crucial for the herbal and Ayurvedic industries. The genetic approach by DNA barcoding plays a pivotal role in accurate species identification, authentication and quality control. Due to various therapeutic properties, Withania somnifera has been used worldwide in traditional systems of medicine for centuries including Ayurveda and Unani. The increasing demand for W. somnifera products has led to concerns regarding the authenticity and quality of commercial herbal preparations. However, adulteration become major trouble for users and industry for safety reasons and authentication of the plant with proper DNA marker is a major concern. METHODOLOGY:DNA barcoding techniques and Phylogenetic analysis were employed to authenticate W. somnifera plant species using universal genetic markers. The markers were PCR amplified, sequenced and analyzed using BLAST-based and phylogeny-based identification methods. RESULTS:The BLAST result shows the percent identity (PI) of ITS1, ITS2, trnK, atpB, rbcL and matK was 100%, 100%, 100%, 97.59%, 100 and 99.20% respectively with the NCBI reference sequence. However, ITS1 and ITS2 show the maximum sequence similarity with W. somnifera of NCBI data. Phylogenetic analysis using NCBI data further supports the role of ITS in the discrimination of W. somnifera from closely related species. CONCLUSION:Therefore, the ITS gene may be considered promising a candidate for DNA barcoding for discrimination of W. somnifera from other species, its authentication and quality control.

Background: Androgenic disorders such as androgenic alopecia is driven by elevated Dihydrotestosterone (DHT) levels, which are regulated by the enzyme 5α-reductase. The inhibition of 5α-reductase can thus be a therapeutic strategy for managing such disorders. This study explores the 5α-reductase inhibitory potential of selected Ayurvedic herbs, namely, Prunus dulcis Mill. (PD), Aloe barbadensis Mill. (AB), Bacopa monnieri (Linn.) Wettst. (BM), Glycyrrhiza glabra Linn. (GG), Emblica officinalis Gaertn. (EO), and Eclipta alba (L.) Hassk (EA). Materials and Methods: Hydroalcoholic and aqueous extracts of the selected herbs were prepared and tested for their efficacy in inhibiting 5α-reductase activity. Finasteride, a known 5α-reductase inhibitor, was kept as positive control. The enzymatic activity was measured by monitoring the consumption of NADPH, the cofactor required for the conversion of Testosterone (T) to DHT. A decrease in NADPH consumption indicates effective inhibition of 5α-reductase activity. The extracts were evaluated based on this biochemical method. Results: EA has shown the highest 5α-reductase inhibitory activity, followed by EO, PD, BM, GG, and AB in decreasing order. Conclusion: The study demonstrates that the selected Ayurvedic herbs possess significant 5α-reductase inhibitory properties, with EA showing the highest potential. These findings suggest that these herbs could be incorporated into hair care formulations and other therapeutic applications aimed at managing androgenic alopecia.

Background: Curcuma longa L., commonly known as turmeric has a long history as a medicinal plant. Ancient medicinal practices have been using it for its potent anti-inflammatory, antioxidant, and antimicrobial activities. The primary phytoconstituent, Curcumin exerts significant influence over skin health and the management of dermatological conditions. Its anti-inflammatory and antioxidant attributes ameliorate skin disorders such as acne and psoriasis. Furthermore, this active compound also facilitates collagen synthesis, thereby contributing to skin revitalization and its overall maintenance. Aim and Objectives: This study aimed to formulate, optimize and evaluate a herbal sustained-release topical hydrogel employing Curcuma longa methanolic extract (CE) for improving skin health. Material and Methods: The phytoconstituents in the CE were screened both quantitatively and qualitatively. Following confirmatory tests and method development, a sustained-release hydrogel containing CE was formulated. Further, the pharmacological properties of an enriched CE were explored by performing various in vitro assays. Results: The CE encompassed qualitative identification of several phytoconstituents and quantitative assessment of curcuminoids. CE also exhibited remarkable anti-oxidant properties and anti-inflammatory attributes. The optimized CE containing sustained-release hydrogel showed approximately 90% drug loading with sustained release over 24 hours along with better sun protective capabilities and wound healing efficacy as compared to the pure extract. Conclusion: This research proposes a formulation of a topical hydrogel with a sustained-release profile for the holistic management of several skin-related diseases.

ETHNOPHARMACOLOGICAL RELEVANCE:This review explores the link between Type 2 Diabetes Mellitus (T2DM) and diabetes-induced Alzheimer's disease (AD). It emphasizes the shared pathophysiological links and mechanisms between the two conditions, focusing on reduced insulin levels and receptors, impaired glucose metabolism, insulin resistance, mitochondrial dysfunction, and oxidative damage in AD-affected brains-paralleling aspects of T2DM. The review suggests AD as a "diabetes of the brain," supported by cognitive enhancement through antidiabetic interventions. It focuses on the traditionally used Indian herbs as a means to manage both conditions while addressing developmental challenges. AIM OF THE STUDY:This study explores the DM-AD connection, reviewing medicinal herbs with protective potential for both ailments, considering traditional uses and developmental challenges. MATERIALS AND METHODS:Studied research, reviews, and ethnobotanical and scientific data from electronic databases and traditional books. RESULTS:The study analyzes the pathophysiological links between DM and AD, emphasizing their interconnected factors. Eight Ayurvedic plants with dual protective effects against T2DM and AD are thoroughly reviewed with preclinical/clinical evidence. Historical context, phytoconstituents, and traditional applications are explored. Innovative formulations using these plants are examined. Challenges stemming from phytoconstituents' physicochemical properties are highlighted, prompting novel formulation development, including nanotechnology-based delivery systems. The study uncovers obstacles in formulating treatments for these diseases. CONCLUSION:The review showcases the dual potential of chosen medicinal herbs against both diseases, along with their traditional applications, endorsing their use. It addresses formulation obstacles, proposing innovative delivery technologies for herbal therapies, while acknowledging their constraints. The review suggests the need for heightened investment and research in this area.

Guduchi/Giloy (Tinospora cordifolia) is declared a national herb of India due to its multiple medicinal properties. Samsamani Vati is also known as Guduchi ghanavati (a concentrated form of decoction of Guduchi stem) the secondary Kalpala (formulation) derived from the primary Kwatha Kalpana (decoction). Samsamani Vati is freely distributed by the Ministry of AYUSH in all states and union territories of India as prophylaxis for COVID-19. The molecular docking of Tinocordicide - a constituent of Guduchi (Tinospora cordifolia) showed significant interruption of the viral RBD and host ACE2 interactions. T. cordifolia, T. crispa, T. sinensis, T. smilacina, T. bakis, and T. sagittata are different species of Guduchi, whereas Tinospora crispa and T.sinensis are hepatotoxic. General people are aware of the use of Samsamani vati/ Guduchi Ghana vati/Giloy and purchase from leading Ayurveda medicine manufacturers in India. Tinosporaside is an immune-modulatory active compound as well as a cholinergic inhibitor. It is an attempt for compare analysis of Samsamani Vati/Guduchi Ghana vati used in the population for the prevention of COVID-19 of government supply and lead Pharmaceutical Company of India. The Samsamani Vati/Guduchi Ghana vati of lead Ayurveda Pharmaceutical and Government Supply. (Dabur, Zandu, Patanjali, Himalaya, Baidyanath and IMPCL) were purchased from the local market and put forth for analysis. Tinosporide is significantly detected in Patanjali, Zandu and IMPCL-manufactured Samsamani Vati, whereas a trace amount of bioactive compound in Dabur and not detected in Baidyanath. The analysis showed that no uniformity of Samsamani Vati/Guduchi Ghana Vati of the competitive brand of India. It is recommended to maintain uniformity of bioactive molecules not only for desired efficacy but also for safety.

Convergence of Ayush/traditional medicines with modern medicines by bringing into effect integration of the two or more systems is the way forward for developing holistic healthcare systems throughout the country, based on the concept of the One Nation, One Health System. Adopting schemes, programs, and strategies for bringing about changes in the education system and medical practice, along with ensuring their implementation at each stratum, will aid in unifying the healthcare systems. Given the existence of medical pluralism in India, it is the need of the hour to amalgamate our ancient traditional knowledge and contemporary medicine to build a system wherein both work in unison to promote good health and confer protection from various diseases and make provision for their management in the best possible manner. The current article discusses the requirements and probable impact of developing such system.

Terminalia arjuna W. A. bark is used as a cardioprotective herb in various traditional preparations. It consists of the oleanane class of triterpenoids as cardioprotective principles. In this study, we have developed and validated a simultaneous estimation method for four isolated triterpenoids and determined their biotransformation in a fermented formulation, Arjunadyarishta. A robust high-performance thin-layer chromatography (HPTLC) method was developed for the separation of arjunic acid, arjungenin, arjunetin and arjunglucoside-I. The mobile phase was optimized as ethyl acetate–toluene–tetrahydrofuran–acetic acid (10:5:4:1, V/V) over pre-coated HPTLC silica gel 60 F254 plates. The HPTLC plate was developed to a distance of 70 mm at 23 ± 4 °C in a chamber previously saturated for 20 min. The method was validated for linearity, accuracy, precision, robustness, limit of detection, limit of quantification and specificity. The correlation coefficients 0.998 to 0.999 of the compounds with average recoveries of 96.25

Ayurveda, an ancient Indian holistic health system, holds increasing significance in global health care. With its natural, personalized approaches, Ayurveda complements modern medicine, catering to a growing demand for comprehensive well-being. The Ayurvedic industry stands at a pivotal crossroads characterized by a blend of favorable circumstances and obstacles, collectively positioned to shape the course of holistic health care. Given the escalating worldwide interest in natural and traditional remedies, there exists an unparalleled opportunity for the industry to amplify its scope and influence. The escalating incorporation of Ayurveda into conventional medical practices and wellness approaches opens new doors for collaborations. Nevertheless, within this landscape of promise, numerous significant challenges also emerge. The intricate tasks of standardizing and regulating Ayurvedic products and protocols persist as indispensable undertakings, crucial for upholding the safety and reliability of Ayurvedic interventions. The limited adoption of new technology and modern dosage forms in Ayurvedic product development has also caused significant hindrances. The duality of technological progress introduces both potential and intricacy, thereby demanding a nuanced equilibrium between tradition and innovation. Moreover, a dire requirement for new Intellectual Property Rights demands a serious discussion and possibly an overhaul of the existing system. This review aims to convey that the future trajectory of the Ayurvedic industry and its contribution to improving world health and well-being will only be determined by the skillful exploitation of these opportunities and the competent handling of the discussed obstacles.

In the scenario of modern health issues, Type 2 Diabetes Mellitus (T2DM) has gained much importance as “adult-onset diabetes” which represents a combination of genetic, environmental, and lifestyle choices. It predominantly shows hyperglycemia or increased blood glucose levels, insulin deficiency, and insulin resistance, which typically characterizes this metabolic disorder whilst manifesting life-threatening complications. This report presents the case of a 55-year-old male with T2DM whose glucose levels were monitored during a period when he was on his prescribed antidiabetic medicines, followed by the addition of an Ayurvedic preparation Diabrishta-21. His glucose summary, obtained by the Continuous Glucose Monitoring (CGM) approach depicts a change in the average value of blood sugar levels and glycated hemoglobin levels, decreasing from 167 to 108 mg/dL, and from 7.4% to 5.4%, respectively. Moreover, the percentage of time the blood glucose levels were in the desired target range increased from 29% to 79%. Thus, Diabrishta-21 in this case report appears to be beneficial in the management of T2DM by aiding in controlling the glucose variability and lowering the blood glucose levels.

It is time to ensure that our products meet global standards. Whatever is the global best; we should make it in India and prove it. For that, our entrepreneur friends have to come forward. Startups too, have to come forth. Hon’ble Prime Minister of India, Shri Narendra Modi Mann Ki Baat- 27 Dec, 2020 Ayush has received tremendous attention in the recent past, and the Government of India has vigorously promoted it both in India and abroad along with Yoga. The honorable Prime Minister of India, right from 2014, has most of the time touched upon the benefit of Ayush for society. Along with increasing popularity and focus, the quality of Ayush products also received desired attention from the government and the industry to keep the system relevant for its global positioning. Quality is a critical parameter in product evaluation for ensuring safety, efficacy, and batch-to-batch reproducibility. It thus plays a significant role in determining a product’s acceptance across the market. The Government of India, in association with several industries, has been on an ongoing mission to set quality as a benchmark for every product under the umbrella of Ayush. This article covers the strategies followed by the Ayush ministry and the self-initiatives of the industry for enhancing the quality of Ayush products. Introduction Our honorable Prime Minister, Shri Narendra Modi, has emphasized Yoga, wellness, and the importance of Ayush for promoting holistic health in our country by sharing his “Mann Ki Baat” since 2014. To cover a larger audience, he has used “Mann Ki Baat” as a platform to share his thoughts. He has tried to instill his messages amongst fellow citizens with empathy through this novel initiative. The Ministry of Ayush, Government of India, has been continuously working towards strengthening all the Ayush systems to bring forth increased awareness and improve international acceptance of goods, services, and products[1]. This will ultimately facilitate a rise in stakeholders’ interests and foster opportunities for sustainable growth of the AYUSH industry[2,3]. The foremost requirement for attaining the above is ensuring ‘quality’ at each step. AYUSH industry has been performing well over the last decade; as per the Research and Information System Report 2021: AYUSH Sector in India: Prospects and Challenges, the growth rate of the total output of the AYUSH industry has outperformed other industries such as Pharmaceuticals, Food and Beverages and Chemical/Petroleum industries.[4,5]. The current turnover of the AYUSH industry is US$ 18.1 billion. It has grown by 17% during 2014-2020, demonstrating tremendous potential in the AYUSH sector[6]. Similarly, during the 87th episode of Mann Ki Baat, Hon. PM addressed that the market of the Ayush Industry is increasing continuously. Six years ago, the market for medicines related to Ayurveda was around 22 thousand crores. Today, the Ayush Manufacturing Industry is reaching around one lakh forty thousand crore rupees; the possibilities are increasing continuously in this sector. In the start-up world, too, AYUSH is becoming a subject of attraction. The quality of any AYUSH product is thus assessed through the quality of raw materials in process control, processing, packaging, finished product, and its distribution in the market[3]. The Ministry of Ayush has taken several measures to implement ‘quality’ as a crucial criterion while developing AYUSH-based products which abide by the GMP guidelines to generate trust and increase awareness regarding the application of various ancient knowledge-based approaches that promote health and well-being across different parts of India[1,7]. The AYUSH ministry also collaborated with World Health Organization (WHO) to deliver the same globally[8]. The article covers the major initiatives taken by the Ministry of Ayush, the Government of India, and the industry to ensure the quality of Ayush products. 1. Initiatives taken by the Ministry of Ayush, Government of India The continuous strive for the growth and upliftment of Ayush products has been a primary focus of the Ministry. The significant initiatives are mentioned below and as mentioned in Fig 1:Fig 1: Summary of the initiatives taken by the Ministry of Ayush in the development and assurance of Quality Products 1.1 Development and implementation of Good Manufacturing Practices (GMP) Schedule T and WHO-GMP guidelines for Ayush drugs[9,10]. 1.2 Certification of Ayush products-Ayush Mark(s)[11,12]. 1.3 Development of Ayurvedic, Unani, and Siddha Pharmacopeia and of “ONE HERB ONE STANDARD”[13,14] through PCIM&H. 1.4 Setting up of National Medicinal Plant Board (NMPB) to develop sustainable cultivation strategies to ensure the availability of quality raw materials[15,16]. 1.5 Initiatives for post-marketing surveillance-Introduction of Ayush Pharmacovigilance[17]. 1.1 Development and implementation of Good Manufacturing Practices (GMP) Schedule T and WHO-GMP guidelines for Ayush drugs In India, State Governments regulate the licensing and quality control of ayurvedic medicines, whereas the legal provisions are devised or amended by the Central Government. Quality standards and Good Manufacturing Practices for Ayurvedic drugs are specified based on the Drugs and Cosmetics Rules, 1945, and Ayurvedic Pharmacopoeia and authoritative books listed in the first schedule of the Drugs and Cosmetics Act, 1940. For the global acceptance of products under the Ayush umbrella, the Ministry, in association with WHO, has implemented WHO GMP for providing Certificate of Pharmaceutical Products (CoPP)[18]. In India, Schedule T, under the Drugs and Cosmetics Act 1940, describes various regulations and requirements for manufacturing (as per GMP) of Ayurvedic, Siddha, and Unani (ASU) products. Schedule T specifies the requirements for hygienic conditions in the factories. Conforming to GMP standards is mandatory for all manufacturers of ASU products[19]. Implementing the GMP government ensures the total quality assurance of Ayush products. Implementation of GMP generates trust in the products manufactured thereby. Moreover, it meets the requirements of several countries requiring GMP-manufactured products for successful imports. Thus, the incorporation of GMP enables manufacturers to export their products. WHO recommends COPP or Certificate of Pharmaceutical Products, and submission of it is mandatory for those countries that import goods or medicines[18]. The primary significance of COPP is that it indicates that the imported drug is of the relevant quality, safety, and efficacy standard. The Ayush marks can now be considered a basis for COPP for Ayurveda, Siddha, Unani, and Homeopathy products issued by the Drug Controller General[24]. Heavy Metal Testing Made Mandatory for Herbal AYUSH products Saper et al. published an article in the Journal of American Medical Association in 2004[23] claiming that fourteen out of seventy Ayurvedic products collected from the US market contained heavy metals. This article led to a series of actions by the then Department of AYUSH to impose stringent conditions on exports and make testing of heavy metals, mercury, arsenic, lead, and cadmium mandatory for all herbal Ayurvedic products not only for exports but for the domestic market also. Ayurvedic Pharmacopoeia recommended testing every product for heavy metals and pesticide residue, aflatoxin, and microbial load before releasing it to the market. This action of the then Department of AYUSH reinforced its focus on the quality and safety of products for consumers. 1.2 Certifications of Ayush products - Ayush Mark(s) The Ministry of Ayush has undertaken an appreciable initiative for certifying the quality of Indian Traditional Medicines or Ayush products so that consumer confidence is increased and facilitates export[12]. For this purpose, the Department of Ayush signed MOU with the Quality Council of India (QCI) on 27th July 2009. QCI has drafted a Voluntary Certification Scheme for Ayush Products (VCSAP)[25] based on the certification criteria. Two certification marks are there for AYUSH products: the ‘AYUSH Standard Mark’ and ‘AYUSH Premium Mark.’ The basis of the AYUSH Standard Mark is compliance with domestic regulatory requirements, whereas AYUSH Premium Mark is based on the WHO GMP requirement and product requirements[25]. A significant contribution of AYUSH marks is providing a visual assessment and recognition tool for the quality of the product, which guides consumers to the product of the Ayurveda industry. These AYUSH marks are regarded as a symbol of trust nationally and internationally. At the same time, AYUSH Marks also helps to gain and increase the reputation and name of the industry in local, national, and international aspects[27]. 1.3 Development of ASU Pharmacopeia The quality of any product is dictated by many statutory bodies like- Ayurvedic Pharmacopeia of India Unani Pharmacopeia of India The Indian Pharmacopeia Bureau of Indian Standards The standardization of Ayurvedic products is an essential factor driving scientific and industrial interests. Invention and selection of appropriate standardization processes for determining consistency, quality, and effectiveness are crucial. With time, changes have been made in the standardization techniques for herbs in the Ayurvedic Pharmacopoeia[28,29]. The Ministry of Health and Family Welfare has published API for the traditional medicinal system, which significantly contributes to the quality assurance of these systems[30]. Since 2010, Pharmacopoeia Commission of Indian Medicine (PCIM), which is now, called Pharmacopoeia Commission of Indian Medicine and Homeopathy (PCIM&H), an apex body of the Ministry of Ayush, Government of India directs Ayurvedic Pharmacopoeia Committee (APC) for quality standards of ASU drugs[28]. In 2021, for further progression of Ayurveda and other Indian traditional medicine systems, PCIM&H has signed an agreement with American Herbal Pharmacopoeia, USA. Challenges like multiple standards for a single herb in a day-to-day workflow have been a pain for the industry to manufacture ASU products. To address this issue, PCIM&H, and Indian Pharmacopoeia Commission, have signed an agreement for developing “One Herb, One Standard,” which clearly shows the sheer sensibility of the Government of India[14,31,32]. 1.4 Setting up of National Medicinal Plant Board (NMPB) for the development of sustainable cultivation strategies to ensure the availability of quality raw material Even though the primary resource of medicinal plants is woodlands, their decreasing rate due to anthropogenic pressure leads to the requirement for alternative sources of medicinal plants. Therefore, the only alternative means to generate more raw materials for herbal medicines could be cultivating medicinal plants on a large scale. The primary initiative taken by the Government of India in this context is establishing National Medicinal Plants Board (NMPB) on 24th November 2000 to coordinate every matter associated with medicinal plants and supporting policies and programs for developing trade, export, conservation, and cultivation as well[33]. [C1] The essential purpose of this government board is to encourage and promote the cultivation of medicinal herbs and management in a sustainable manner throughout the country so that the collection of herbs from wild sources can be reduced. In addition, NMPB has also encouraged research and development, developing and strengthening capacity through training and increasing awareness. By developing Good Agricultural and Collection Practices, agro-techniques, monographs prescribing standards of quality, safety, and efficacy, and credible instituting a mechanism for certification of quality of raw drugs, seed, or other planting material, NMPB encourages quality assurance and standardization of herbal drugs[33]. A Central Sector Scheme has been launched for the conservation, development, and sustainable management of medicinal plants to prevent destructive harvesting and the threat of extinction of herbal species, which ultimately would prevent the chances of mixing of substitutes or adulterants, which can affect the quality of the herbal preparations in terms of safety and efficacy[35]. This scheme aims to secure the sustained availability of quality herbs and herbal raw materials by in-situ and ex-situ conservation of endangered herb species that are considered crucial components of the AYUSH medicinal system. 1.5 Initiatives for post-marketing surveillance-Introduction of AYUSH pharmacovigilance The Ministry of Ayush, along with the Institute for Post Graduate Teaching and Research in Ayurveda, Jamnagar, under the Central sector scheme for upgradation to the Centre of Excellence, launched National Pharmacovigilance Programme in 2008. From there onwards, this body is responsible for reviewing and analyzing the adverse drug reaction reports at different levels in ASU products[38]. This center has been shifted to the All India Institute of Ayurveda in New Delhi. 2. Initiatives by the Industry Going beyond regulatory requirements, the industry has come forward with innovative strategies and cutting-edge technologies across its diverse functional areas to maintain and promote ‘quality’ at every step of product development, manufacturing, and control. [Figure 2] depicts the initiatives taken by the industry, and they are mentioned below:Fig 2: Schematic elucidation of Industrial Initiatives for establishing Quality Products at a glance. 2.1 Adoption and incorporation of technology at various steps for manufacturing 2.2 Utilization of modern analytical techniques for quality control[39] 2.3 Use of the latest biotechnology tools for efficacy and safety determination 2.4 Development of platforms promoting digitization[40] 2.5 Shelf life Determination of ASU drugs[41] 2.6 Role of packaging in the quality of AYUSH drugs[42] 2.1 Adoption and incorporation of technology at various steps for manufacturing Developing a product with quality as a top priority has always been challenging for industries. However, rapid advancement in technology and infrastructure has provided space for the industry to meet this challenge and deliver high-quality products. There are multiple aspects where the industries have put forward their contribution jointly with the AYUSH ministry to set a benchmark. The regulatory guidelines and initiatives, a framework by the Ayush ministry, have provided a substantial guide to the industries for designing and manufacturing quality products. The first initiative that the industry has implemented is automation[43]. The elimination or minimization of manual interference in product sampling and quality checks has increased the workflow and rapidly minimized the chances of contamination with the overall upgradation of finished products. Automation at every step, from raw materials management with advanced tracking systems to post-sales vigilance of the finished products. 2.2 Utilization of modern analytical techniques for Quality Control Industries have developed cutting-edge analytical technology, from raw herbs identification and sampling to quality checks of the finished products, including HPLC, HPTLC, GC-MS, LC-MS, thermal analytical methods like thermogravimetric analysis (TGA), differential thermal analysis (DTA), and differential scanning calorimetry (DSC)[29] that have been employed to study any physical or chemical changes in Ayurvedic medicinal products and also used to study pre-formulation or drug excipient compatibility. Near-infrared spectroscopy (IR Spectroscopy) technique has been used to quickly determine active components, species, unique medicinal formulae, in-process quality control, identification of counterfeit, and discrimination of geographical origins of the plant species. Thus, the identification and standardization of polyherbal Ayurvedic formulations by these technologies have also been a contribution by the industries[44] The DNA fingerprinting technique, the latest gold standard tool, has been adopted by industries to eliminate the adulteration of plant species. This has been possible through the identification of intra-generic and intra-specific DNA markers of different Ayurvedic herbs[45] Similarly, for bhasma, the Ayurvedic metallic preparations in which metal acts as a carrier for drug delivery, which is widely recommended for treating various chronic ailments, various high-end techniques like X-ray diffraction analysis (XRD), Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), and Energy Dispersive Spectroscopy[47] have been employed for the estimation and characterization. Techniques like neutron activation analysis of calcium, iron, zinc, and mercury., confirmed the purity of bhasma. Recently, the utilization of microfluidic analytical devices for drug analysis has been adopted by industries. This technique offers several advantages, such as simplicity, low cost, rapid analysis, portability, and low reagent and sample consumption, thus creating a high-throughput platform with robust applicability. 2.3 Use of the latest biotechnology tools for efficacy and safety determination The industry has developed modern biotechnological tools to validate the biological efficacies of Ayush products which have been a milestone achievement in the determination of the biological effects of the already-known traditional Ayurvedic herbs. Such signature initiatives involving the comprehensive amalgamation of chemistry and biology at various research-oriented Ayush pharmaceutical industries have set up a benchmark for developing quality products. [C2] 2.4 Development of platforms promoting digitization One of the crucial aspects of quality product development is the document management system. Ayush ministry has given guidelines for proper documentation at each level of product development to ensure traceability and data authenticity. The industries have equally contributed to abiding by the guidelines in taking various constructive strategies. The introduction of an electronic documentation system has changed the scenario of tracking and channeling data in a highly organized manner. The electronic laboratory notebook (eLNB) system has been a boon to industries that helps in real-time documentation and data tracking. The unification of automated technologies for minimal human errors, high-throughput analytical techniques, and the latest IT infrastructure for proper documentation and storage has been the industry’s thrust areas to contribute and develop quality products. 2.5 Shelf-life determination of ASU drugs A product’s shelf life is a crucial aspect of quality determination and relies on the packaging. The principal reason for stability testing is that the drug is safe and efficacious for patients. Moreover, it is a legal requirement that should be provided to the regulatory agencies to approve the drug or formulation. Stability studies ensure that the drug retains its mentioned functionality as long as it is available in the market. 2.6 Role of packaging in the quality of Ayush drugs Packing of the product plays a crucial role in maintaining the stability of the product, thus, increasing and maintaining the shelf life of a product. Ayush products include churna or powder, tablets, capsules, and avaleha (electuary). Historically AYUSH products were delivered through Vaidya (Ayurvedic physician) in conventional packaging, i.e., packing a single dose in a paper wrap or glass bottles for liquid. As evolution took place through industrialization, many renowned companies started making Ayush products commercially. Packaging played a critical role in designing and delivering packaging formats suitable for production lines and providing the required shelf life to products. It helped the industry offer better consumer packaging, which can ease dosage/usage[49]. Majorly Ayush product contains natural herbs, and sometimes the formulation is highly sensitive to moisture, oxygen, heat, and light, which impacts the product’s texture, shelf-life, odor, and taste. Packaging has two primary functions, namely containment, and protection. Regarding containment, the package protects the product from being exposed to the environment; for protection, the product does not sustain any physical damage. The product and package must maintain a drug’s integrity and effectiveness from manufacturing to consumption. The foremost packaging requirement in this context is to protect the drug from chemical degradation. The bulk package used during manufacturing should not react with the drug being manufactured until the drug is consumed. It is one of the biggest tasks of the packaging material to maintain the shelf life of the product. The other protective functions of excellent packaging are sterility, re-closure, communication (via the label), compliance, tamper evidence, and temperature control. The technology of packaging a drug is a demanding and growing industry. There is a continuous requirement for the diverse area of package, design, development, and engineering. There is an ongoing change and re-alignment with developing newer technologies, drugs, and delivery systems[49]. Traditional Ayurvedic practices influence the packaging design for AYUSH products. The packaging is generally designed with earthy tones and natural textures to convey the natural and organic nature of the product. The packaging also includes images of herbs and plants to emphasize the natural ingredients used in the product. The packaging also includes information about the product, such as the ingredients used, the dosage, and the product’s benefits. To summarize, packaging plays a significant role in defining the quality of the AYUSH products by protecting and preserving the product, providing information, branding, ensuring compliance with regulations, enhancing the consumer’s perception of the product’s quality, and improving the overall experience of using AYUSH products. The packaging for AYUSH products in India is influenced by traditional Ayurvedic practices and is designed to be eco-friendly and biodegradable; some contemporary dosage forms of ASU products are shown in Fig 3. There is a trend toward using modern packaging materials like plastic and aluminum, but some companies are addressing environmental concerns by using biodegradable plastics and recyclable materials. The packaging design includes earthy tones, natural textures, and images of herbs and plants to convey the natural and organic nature of the product.Fig 3: Contemporary dosage forms of ASU productsCurrent status The Ayush ministry has implemented rule 161 B to mention the expiration date of Ayurvedic, Siddha, and Unani medicines and proposed for the shelf life of the Ayurvedic formulations as mentioned earlier after the issuance of the gazette notification by the Government of India on 20th October 2009, a modified draft notification of the same issued on 26th November 2005[19]. Need gap analysis It has been well explained that packaging materials play a vital role in maintaining and increasing the shelf life of any product, but the guidelines available in AYUSH need to clearly mention the type of packaging required for the different types of formulations. To maintain the shelf life of different formulations mentioned in section 3 of rule 161-B, the ASU industries have to make their in-house guidelines regarding the packaging. The selection of a package often begins with determining the product’s physical and chemical characteristics, protective needs, and marketing requirements. The materials selected must have the following characteristics: They must protect the preparation from various hazards (physical, climatic, chemical, and biological), and they must not be reactive with the product. It must be compliant with the current Good Manufacturing Practices [C3] (cGMP) regulations), must not impart to the product tastes or odors, and must be nontoxic[19,41]. Initiatives on Packaging of ASU drugs To keep up with the advancements in the pharmaceutical industry, AYUSH industries are putting their efforts with the help of their Research and Development team to increase and maintain the stability and shelf life of their products following the guidelines. Due to the lack of packing guidelines, industries face multiple difficulties. Quality of packaging maintains the integrity of the Ayurvedic products during storage, shipment, and delivery. So, development in the packaging field correlates with the development of newer products. Software and technology services will significantly accelerate packaging design for Ayurvedic products. Cost and time-effective packaging technology need to be enhanced in Industry. Packaging should be patient-compliant as well, with proper labeling. Manufacturers involved in packaging for the self-drug administration process need to provide delivery systems that will simplify drug reconstitution before use, especially for nonprofessional caregivers. This will further increase the rate of launching a product in the market[50]. 3.0 Summary Quality is one of the essential factors in harnessing global opportunities. During the recent pandemic of COVID, Ayush products have shown their potential to strengthen immunity and imparted a massive increase in overall wellness, which displays that quality plays a pivotal role in product efficacy. Moreover, adopting the latest technologies like DNA fingerprinting for raw materials evaluation, biological assays for ensuring efficacies, and mass spectroscopy for particle size analysis have pushed quality parameters high. In keeping up with the modern pharmaceutical industries, the Ayush Ministry has shown diligence in introducing post-marketing surveillance of their products by vigilance, also known as ‘AYUSH pharmacovigilance.’ We hope that all the quality augmentation steps by the Ministry of Ayush as well as the industry will make the dream of our honorable Prime Minister of taking Yoga and Ayurveda to a global pedestal would be realized in its harmony. 4.0 Future Perspective The pace of evolution for AYUSH across the globe has been remarkable past few years. This has been possible through the combined efforts of the Ministry of Ayush and the collaborating industries. The unanimous goal is to establish AYUSH products in India and the global markets. This has highlighted the ancient science of our motherland and the upliftment of traditional knowledge in the pan-scientific world. Thus, the industries have taken multiple approaches related to chemical, analytical, and manufacturing processes. Industrial influences have modernized the concept of packaging related to AYUSH products. Likewise, advancement in digitization and the latest technology adoption and implantation, abiding by the legal laws and guidelines will not only create a massive revolution in the AYUSH product markets but also create awareness and more acceptance. With the advent of artificial intelligence (AI) in the 21st century, the global markets have witnessed a tech boom, which the industries shall certainly explore to augment the quality standards of the products not only at the manufacturing level but also in their execution. This crucial juncture calls for unified and synchronized efforts of the Ministry of Ayush and industries to take Ayush to newer heights to provide the global stature it deserves. 5.0 Acknowledgment The authors acknowledge the contribution of the scientists at Emami Healthcare and Packaging R&D Divisions in Kolkata. Financial support and sponsorship Nil Conflicts of interests There are no conflicts of interest.

Abstract BACKGROUND: A densitometric High Performance Thin Layer Chromatography (HPTLC) method has been established for simultaneous quantification of Gallic acid, Piperine, and Withaferin A in Chyavanprash . Chyavanprash possesses multiple health benefits including immunity boosting and has been widely used since ancient times. The surge of COVID-19 has further increased its demand resulting lack of monitoring on raw materials to ensure its efficacy. METHODS: Aluminum plates coated with silica gel 60 F 254 as stationary phase was used with Toluene:Ethyl acetate:Formic acid:Methanol [30:30:8:2] (v/v/v/v) as mobile phase. The plates were developed to a distance of 60 mm at 25 ± 2°C in a chamber previously saturated for 30 min. Densitometric analysis was performed at 254 nm in absorbance mode. RESULTS: Amounts of Gallic acid, Piperine, and Withaferin A are 0.75% (w/w), 0.28 % (w/w), and 0.14% (w/w), respectively, in the formulation. The method was validated for specificity, linearity, precision, repeatability, and accuracy. Calibration plots were linear in the concentration range 0.5–6.0 µg per band for Gallic acid; 0.20–1.00 µg per band for Piperine, and 2.0–8.0 µg per band Withaferin A. The correlation coefficients were 0.990, 0.994, and 0.997 for Gallic acid, Piperine, and Withaferin A, respectively. CONCLUSION: The method is simple, precise, specific, accurate, and economical. It can be used for routine analysis in formulations containing Amalaki , Pippali , and Ashwagandha .

EDITORIAL article Front. Pharmacol., 10 November 2022Sec. Ethnopharmacology https://doi.org/10.3389/fphar.2022.989934

Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi, India, Emami Ltd., Kolkata, India, Medical Clinic III, AG Synergy Research and Experimental Medicine, University Hospital Bonn, Bonn, Germany, School of Natural Product Studies, Jadavpur University, Kolkata, India, Institute of Bio-Resources and Sustainable Development (IBSD), Imphal, India

Trigonelline (TR), 4-hydroxyisoleucine (4-HI), and diosgenin (DG) are the main bioactives of the purified standardized extract of the popular plant Trigonella foenum-graecum L. (TFG), and it has been proven effective for the treatment of various diseases. However, to the best of our knowledge, no study has investigated the pharmacokinetic parameters of purified standardized T. foenum-graecum extract in normal and diabetic Wistar rats. The present study has developed and validated a rapid, reliable, and sensitive simultaneous ultra-performance liquid chromatography MS method to estimate these bioactives. The chromatographic separation was achieved using methanol, acetonitrile, and 0.1% formic acid with the ideal gradient flow system on a BEH Shield RP 18 column. A positive electrospray ionization mode was selected to estimate m/z values of TR (138.14 > 94.63), 4-HI (148.19 > 74.08), and DG (415.54 > 271.33). The method was robust and reproducible over the linearity range of 60-5000, 6-5000, and 15-5000 ng/mL for TR, 4-HI, and DG, respectively. Using this novel validated method, we investigated the pharmacokinetic parameters of bioactives using Phoenix WinNonlin version 8.0 (Certera) in normal and diabetic rats. The assay was successfully applied for the estimation of pharmacokinetic parameters using noncompartmental analysis. This investigation shows that the absorption rate increased, whereas distribution and elimination processes slowed down in diabetic rats compared with normal rats.